Topological restriction of SNARE-dependent membrane fusion.

Abstract	To fuse transport vesicles with target membranes, proteins of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) complex must be located on both the vesicle (v-SNARE) and the target membrane (t-SNARE). In yeast, four integral membrane proteins, Sed5, Bos1, Sec22 and Bet1 (refs 2-6), each probably contribute a single helix to form the SNARE complex that is needed for transport from endoplasmic reticulum to Golgi. This generates a four-helix bundle, which ultimately mediates the actual fusion event. Here we explore how the anchoring arrangement of the four helices affects their ability to mediate fusion. We reconstituted two populations of phospholipid bilayer vesicles, with the individual SNARE proteins distributed in all possible combinations between them. Of the eight non-redundant permutations of four subunits distributed over two vesicle populations, only one results in membrane fusion. Fusion only occurs when the v-SNARE Bet1 is on one membrane and the syntaxin heavy chain Sed5 and its two light chains, Bos1 and Sec22, are on the other membrane where they form a functional t-SNARE. Thus, each SNARE protein is topologically restricted by design to function either as a v-SNARE or as part of a t-SNARE complex.
Authors	F Parlati, J A McNew, R Fukuda, R Miller, T H Söllner, J E Rothman
Journal	Nature (Nature) Vol. 407 Issue 6801 Pg. 194-8 (Sep 14 2000) ISSN: 0028-0836 [Print] England
PMID	11001058 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	BET1 protein, Zea mays BOS1 protein, S cerevisiae Carrier Proteins Liposomes Membrane Proteins Plant Proteins Qa-SNARE Proteins Qb-SNARE Proteins R-SNARE Proteins Receptors, Cell Surface Recombinant Fusion Proteins SNARE Proteins Saccharomyces cerevisiae Proteins Sec22 protein, S cerevisiae Sed5 protein, S cerevisiae Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins Vesicular Transport Proteins N-Ethylmaleimide-Sensitive Proteins
Topics	Carrier Proteins (metabolism) Endoplasmic Reticulum (metabolism) Escherichia coli Golgi Apparatus (metabolism) Liposomes Membrane Fusion Membrane Proteins (chemistry, metabolism, physiology) N-Ethylmaleimide-Sensitive Proteins Organelles (metabolism) Plant Proteins (metabolism) Protein Conformation Qa-SNARE Proteins Qb-SNARE Proteins R-SNARE Proteins Receptors, Cell Surface (metabolism) Recombinant Fusion Proteins (metabolism) SNARE Proteins Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins Structure-Activity Relationship Vesicular Transport Proteins

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